Research

We are now at a point where the CF Foundation and drug companies have many potential compounds ready to become new medicines.

However, we may not know whether they are good or not because not enough people are volunteering to take part in research! Check out www.cff.org/research; especially check out the Drug Development Pipeline.

We all eagerly await new medications to take care of you or your child. Finding these new drugs, proving that they are safe and proving they are effective, is what research is all about. Without research we would not be able to improve the lifespan or the lives of people with CF. But research is more than just the science, research is a gift given to us by those who have gone before. We use today's medicines because someone else took part in the research trials to prove them.

In 2003 only approximately 1000 people with CF took part in research trials. Two years ago, 3,000 people joined up. But by next year, it is estimated that double that number, or 6,000 people with CF will be needed to help investigate what drugs really work.

Here is a quick review of the research process. Before a new drug or therapy becomes available to the CF public it first is tested in vitro - meaning in test tubes, cultures, on the molecular or cellular level. It is then tested in animals. Only after these initial evaluations show some promise, does testing begin in humans. There are then 3 stages of research before a drug can be prescribed. Phase 1 research looks at safety of the drug when given to volunteers (CF and non-CF). If it passes this phase, then Phase 2 research continues to look at safety in even larger numbers of CF patients. Phase 2 trials also help to determine the best dose and frequency of treatment. Although these early studies may look to see if the treatment helps to improve CF, only pivotal Phase 3 studies have enough patients and detail to determine if a new treatment makes a real difference.

The Central CT CF Center has done research sporadically in the past, including intravenous antibodies, Pulmozyme, Synagis, airway clearance, and a new inhaled antibiotic, Aztreonam, which will soon be approved and become a significant player in our CF therapies.

Research Studies at CCCFC

Two years ago, your CF Center recognized that we needed to do more. The CCCFC applied for and received a research facilitation grant in 2006 from the Cystic Fibrosis Foundation. This grant has helped us to improve our support systems so we are now able to do more research.

Since then we have participated in a multi-center, Phase 3 study on Denufusol (the TIGER study). This is one of the first new medicines that takes aim at correcting the basic defect in CF airways! The CF defect is actually a defect in a chloride ion channel in the cell. Denufusol helps to stimulate an alternate chloride channel. In other words, if we can get more chloride out into the airway using a non-CF channel we may be able to partially normalize the CF airways, making it easier to produce and move mucus! The preliminary studies (Phase 1 and 2) look very promising, especially for people whose CF is still relatively mild. Our study looked at this mild CF group to maximize the chance of seeing a positive effect - people 6 to 21 years old, with normal to mild decreased PFTs (FEV1 greater than 75%). We began this study with seven patients and ended it with five and have now completed our participation in this study Once this study is over (we have to wait until all the CF sites taking part in are finished), the results from all of the participating CF centers will be analyzed. If they are good, the drug may be approved and there are plans to look at it in people with more significant disease.

We are currently finishing a multi-center, Phase 3 trial on azithromycin, with ten patients taking part. This is a common antibiotic used for many things. It has already been proven to significantly improve PFTs and decrease exacerbations (times of increased respiratory symptoms) in CF people who have Pseudomonas aeruginosa. What we don't know is whether it will help people with CF before they have Pseudomonas. That is what we are looking at currently. Azithromycin is given once-a-day, Monday, Wednesday, and Friday.

The Adult Program is starting a study looking at dry-powdered inhaled tobramycin. A drug company has made tobramycin that is essentially given by an inhaler! In other words, it will take just a minute or two to do a whole treatment instead of the 20 minutes it takes currently. This study requires patients to already have Pseudomonas aeruginosa, and to have at least mild to moderate decrease (FEV1 less than 75%). Most of our pediatric patients' PFTs are too high to qualify for this study.

We will soon be taking part in another study of inhaled aztreonam. The earlier study was pivotal, and showed inhaled aztreonam worked in mild to moderate CF (i.e. FEV1 between 40 - 75%) with Pseudomonas. Now we want to see if it helps people who have Pseudomonas, and a minimal decrease in PFTs (i.e. normal or FEV1 greater than 75%). The exciting thing about this study is that we know inhaled antibiotics generally help and this antibiotic only takes 2 minutes to use. To take part in this study, you need to be older than six and have an FEV1 greater than 75% of predicted.

We will also be looking at inhaled Mannitol. This is also a dry-powdered inhaler, taken twice a day that may make secretions easier to move. Mannitol may increase the thin fluid layer that mucus floats on, or it may make the mucus thinner. If either is true, mucus should be easier to move. In theory, mannitol is similar in a way to hypertonic saline, pulmozyme, or even the other medicine we looked at, Denufusol. To participate people must be older than 6, and have PFTs (FEV1) between 40 and 80%.

Participation in these clinical trials is voluntary, but absolutely necessary for a drug to be approved by the FDA. To know whether a medicine works, most research studies are randomized and controlled, that means some people in the study receive a harmless, fake medicine (the control or placebo). Most studies also understand people want to get the new medicine, so for the first half of the study some people will get the control, but during the second half, everyone gets the study medicine. Most studies are also 'blinded'. That means that neither the person taking the medicine OR your CF team knows who is getting real medicine.

We ask you to think about clinical research trials, and where they may fit into your life with cystic fibrosis. We will keep you updated during clinic visits and on our website. We hope many of you will be interested in participating in finding the cure for CF. If you have any questions, please do not hesitate to contact us at the CCCFC (email ucccfc@connecticutchildrens.org, call either Ginny, our pediatric research coordinator at 860-545-9440 or Sandy, our adult research coordinator at 860-972-3416, or speak to any of us during clinic).